Psoriasis: Screen for Fatty Liver Before MTX?

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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

CHICAGO -- What began as a case of chronic plaque psoriasis has evolved into consideration of routine testing for nonalcoholic steatohepatitis (NASH) before initiating methotrexate, according to a British study.

The growing prevalence of risk factors for fatty liver disease and NASH warrants consideration of routine screening of at-risk patients, such as those with diabetes, obesity, and hypercholesterolemia. In England, specialists have begun considering strategies to evaluate such patients prior to starting methotrexate for psoriasis, Arpita Debroy Kidambi, MD, of Royal Hallamshire Hospital in Sheffield, said here at the American Academy of Dermatology summer meeting.

"Currently, a third of the population in the U.K. is affected by nonalcoholic fatty liver disease [NAFLD] and 2% to 5% by NASH," Debroy Kidambi said. "Prevalence of risk factors for fatty liver disease continues to increase, not only in the U.K. but throughout much of the world."

No consensus exists about how to approach the problem, but ultrasound and fibroscanning have received consideration as potential screening techniques, she added.

Routine screening for NAFLD or NASH runs counter to current clinical recommendations and practice in the U.S., said Mark Lebwohl, MD, of Mount Sinai Hospital in New York City. The guidelines do not eliminate consideration of a liver biopsy, but that consideration comes only after a patient has been on methotrexate for awhile.

"In the old days, we actually used to require liver biopsies before starting methotrexate," Lebwohl, who co-authored the AAD clinical recommendations, told MedPage Today. "It turned out that most of those liver biopsies showed no damage, and we were putting patients at risk of a significant procedure."

Several serologic tests have been developed, but none has proved to be foolproof for detecting fibrosis or NASH, he added.

The issue of screening patients with psoriasis for NAFLD and NASH arose during a review of medical records for a patient who had no risk factors for fatty liver disease when he started methotrexate. After several years of effective treatment, routine lab work showed the patient had elevated levels of pro-collagen N-terminal propeptide III (PIIINP). Levels of the marker for liver fibrosis increased gradually, reaching a maximum of 8 mcg/L.

The rise in PIIINP levels coincided with the patient's development of risk factors for fatty liver disease, notably obesity and diabetes.

Following British Association of Dermatology recommendations regarding persistently elevated PIIINP, the patient's medical team performed a liver biopsy. The specimen revealed severe steatosis and extensive zone III fibrosis.

"The findings were consistent with active nonalcoholic steatohepatitis," said Debroy Kidambi. "The findings were thought to be potentially related to methotrexate, which was subsequently stopped. Cyclosporine was initiated, and risk factors such as high body mass index and newly diagnosed diabetes were aggressively managed."

The case illustrated a need to consider how best to approach the issue of psoriasis, methotrexate, and fatty liver disease, she continued. Although the liver disease ultimately was detected and managed effectively, identification and treatment prior to development of fibrosis would have been preferable.

Increasingly, clinicians who treat psoriasis in England have begun discussing noninvasive methods to evaluate patients for fatty liver disease, Debroy Kidambi said. Liver biopsy obviously is the most definitive approach but is invasive and not without risk. Much of the discussion has focused on ultrasound and fibroscanning.

"Initially, we were thinking about performing ultrasound on all at-risk patients," she told MedPage Today. "We didn't have as much sense about fibroscanning at the time. We have since talked with hepatologists who have considered doing fibroscanning on a regular basis."

Discussions have not yet reached the point of screening intervals or what to do about at-risk patients already on methotrexate. Debroy Kidambi did not know how much screening studies would add to the cost of caring for patients with psoriasis.

Lebwohl agreed that many at-risk patients can be identified by clinical factors, but the AAD guidelines recommend a course of action that does not include imaging studies or scans.

"The guidelines have a list of predisposing factors that can be used to identify patients who are at risk," he said. "Basically, if a patient has any of those factors, the guidelines suggest considering an alternative treatment or perform a liver biopsy. However, a liver biopsy is not necessary before starting methotrexate."

"A liver procedure is a serious procedure. What if you go on methotrexate and you don't tolerate it? What if you go on methotrexate and it just doesn't work for you? For patients with risk factors for NASH, we recommend a liver biopsy 2 to 5 months after starting methotrexate so that we know the drug is working and it's tolerated."

For patients without risk factors for fatty liver disease, the AAD recommends periodic liver function tests. As long as the test results remain normal, a liver biopsy is not indicated, Lebwohl added.

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